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myChoice CDx® Technical Information bit.ly/myChoiceCDxSpecs
1 MGL CDxDC 0210 REV 3
Myriad Genetic Laboratories, Inc.
320 Wakara Way, Salt Lake City, UT 84108
Phone: 1-877-283 6709
www.myriad.com
Intended Use
Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that
assesses the qualitative detection and classification of single nucleotide variants, insertions and
deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries
of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS)
which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic
Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-
fixed paraffin embedded (FFPE) tumor tissue specimens.
The results of the test are used as an aid in identifying ovarian cancer patients with positive
homologous recombination deficiency (HRD) status, who are eligible, because of a positive test
result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may
become eligible, because of a positive test result for deleterious or suspected deleterious
mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with
the targeted therapy listed in Table 1 in accordance with the approved therapeutic product
labeling.
Table 1: Companion diagnostic indications
Tumor Type Biomarker Therapy
Ovarian Cancer Myriad HRD (defined as deleterious or
suspected deleterious mutations in
BRCA1 and BRCA2 genes and/or
positive Genomic Instability Score)
Lynparza® (olaparib)
Zejula® (niraparib)
Detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive
Genomic Instability Score in ovarian cancer patients is also associated with enhanced
progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy. This assay is for
professional use only and is to be performed only at Myriad Genetic Laboratories, Inc., a single
laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.
Contraindication
• There are no known contraindications.
Warnings and Precautions
• There are no known warnings or precautions.
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Limitations
• For in vitro diagnostic use
• For professional use only
• For prescription use only
• This test identifies germline and somatic variants in the tumor but does not distinguish
between the two.
• Reduced hybridization efficiency of DNA fragments spanning long insertions and
deletions (indels) or rearrangements may result in under-representation of mutant DNA
molecules in the final sequencing library. This will result in a reduction in the observed
frequency of sequence reads spanning the mutation
• Indels > 25 bp in length can be detected by this assay. However, the ability to detect
any particular indel may be impacted by the location and nature of the mutation, the local
sequence context, the DNA quality, and the non-tumor DNA content in the sample
provided.
• This test has been designed to detect genomic rearrangements including
large rearrangements (LRs) involving the promoter and coding exons
of BRCA1 and BRCA2, however, the detection of large rearrangement deletions and
duplications is dependent on the quality of the submitted specimen.
• Whole gene duplications and deletions may not be detected by the myChoice CDx assay.
• Other terminal duplications are reported as variants of uncertain significance.
• This analysis is believed to rule out the majority of abnormalities in the
genes analyzed. There may be uncommon genetic abnormalities such as specific
insertions, inversions, and certain regulatory mutations that will not be detected by
the myChoice CDx assay. Test Principle
The myChoice CDx test determines a patient’s Myriad HRD Status by detecting single
nucleotide variants (SNVs), variants in homopolymer stretches, indels, and LRs in the BRCA1
and BRCA2 genes and determining a GIS using DNA obtained from FFPE ovarian tumor tissue.
A positive Myriad HRD Status result is due to either the presence of a pathogenic mutation in
BRCA1 and/or BRCA2 (sequencing and/or LR) [tBRCA1/2 Status] and/or a GIS above a defined
threshold [GIS Status].
The assay employs a single DNA extraction method from FFPE specimens, 30-200 ng of which
undergoes multiple steps including fragmentation, end repair and adenylation, adapter ligation,
library construction/amplification, hybridization and capture, sequencing and data analysis.
The myChoice CDx test is composed of the following major processes:
• Tumor Sample Collection and Shipping
• Tumor genomic DNA Extraction
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• DNA Processing using the following assays:
o myChoice CDx next generation sequencing is used to detect sequence variants and
genomic rearrangements (ie. large deletions and duplications) in BRCA1 or BRCA2,
and genomic instability analysis
• BRCA1 and BRCA2 Variant Classification
• Genomic Instability Calculation (GIS)
• Results Reporting Summary and Explanation
The myChoice CDx device is a companion diagnostic for Lynparza® (olaparib) or Zejula®
(niraparib), a poly ADP-ribose polymerase (PARP) inhibitor. Patients whose tumors have a
positive GIS Status and/or pathogenic variants in BRCA1 or BRCA2 show improved progression
free survival when treated with Zejula® (niraparib) compared to placebo in the treatment setting.
Test Kit Contents
A sample collection kit provided by Myriad is used by the ordering laboratories/physicians. The
collection kits contain the following components:
• Slide Container
• Tumor Block Container
• Collection Instructions
• Mailing Instructions
• Ice Pack
Instruments
The myChoice CDx device is intended to be performed with the following instruments, as
identified by specific serial numbers:
• Eppendorf MasterCycler PRO-S 96 well Thermocycler
• Illumina HiSeq 2500 Next Generation Sequencer
Sample Collection and Test Ordering
To order myChoice CDx testing, the Test Request Form (TRF) included in the test kit must be
fully completed.
Please refer to the myChoice CDx Collection Instructions and Mailing Instructions for further
details about collecting formalin-fixed paraffin-embedded (FFPE) tumor samples and mailing the
samples to Myriad.
Test Results and Interpretation
Patients evaluated with the myChoice CDx test that have clinically relevant tumor genomic
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instability and/or have been determined to carry a deleterious or suspected deleterious BRCA1 or
BRCA2 mutation can be considered for treatment with Lynparza® (olaparib) or Zejula®
(niraparib) under the supervision of a physician.
Upon completion of testing at Myriad, a test report will be sent to the designated physician. The
results of each test component, along with the interpretation of the BRCA1 and BRCA2
variant(s) identified, are provided. If multiple variants are detected, the overall test interpretation
most relevant to patient management is based on the most severe variant identified. Standard
interpretative information included in test reports is listed below. Note that variants determined
to have a classification of favor polymorphism or polymorphism are not included on the test
report.
myChoice CDx Components:
The overall results are composed of two major components, namely GIS Status, and tBRCA1/2
Status. The combined results form the basis of an overall interpretation of the myChoice CDx
Myriad HRD Status. Potential results for these two components are described below:
“GIS Status: Positive”
The test results demonstrate homologous recombination deficiency based on the GIS alone.
“GIS Status: Negative”
The test results demonstrate homologous recombination proficiency based on the GIS alone.
“Tumor Mutation BRCA1/BRCA2 Status (tBRCA1/2 Status): Positive for a Clinically
Significant Mutation”
The test results demonstrate the presence of a deleterious or suspected deleterious sequencing
mutation or large rearrangement.
“Tumor Mutation BRCA1/BRCA2 Status (tBRCA1/2 Status): Negative for a Clinically
Significant Mutation”
The test results do not demonstrate the presence of a deleterious or suspected deleterious
sequencing mutation or large rearrangement in BRCA1 or BRCA2. This category includes
genetic variants for which published data demonstrate absence of substantial clinical
significance and truncating mutations in BRCA2 that occur at and distal to amino acid 3.326
(Mazoyer S et al., Nature Genetics 1996, 14:253-254). It also includes variants in the protein-
coding region that neither alter the amino acid sequence nor are predicted to significantly
affect exon splicing, and base pair alterations in non-coding portions of the gene that have
been demonstrated to have no pathogenic effect on the length or stability of the mRNA
transcript. There may be uncommon genetic abnormalities that will not be detected by
myChoice CDx testing (see Limitations).
Interpretive Criteria
A positive Myriad HRD status is defined as the presence of deleterious or suspected deleterious
mutation(s) in the BRCA1 and/or BRCA2 genes and/or a positive Genomic Instability Score. The
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interpretive criteria are based on the following classification categories:
“Deleterious”: Includes most nonsense and frameshift mutations that occur at/or before the last
known deleterious amino acid position of the affected gene. In addition, specific missense
mutations and non-coding intervening sequence (IVS) mutations are recognized as deleterious
on the basis of data derived from linkage analysis of high-risk families, functional assays,
biochemical evidence, statistical evidence, and/or demonstration of abnormal mRNA transcript
processing. Deletions and duplications of an entire exon(s) identified by the myChoice CDx test
may also be interpreted to be deleterious. Deleterious large genomic rearrangements include
single exon and multi-exonic deletions that are out-of-frame. Out-of-frame single or multi-exonic
duplications are classified as deleterious if the orientation is determined to be in tandem and
head-to-tail. In- frame deletions/duplications are interpreted on an individual basis and the
specific evidence supporting the classification of these mutations is included in the individual
patient report.
“Suspected Deleterious”: Includes genetic variants for which the available evidence indicates a
high likelihood, but not definitive proof, that the mutation is deleterious. The specific evidence
supporting an interpretation will be summarized for individual variants in the patient report.
“Genetic Variant of Uncertain S ignificance”: Includes missense variants and variants that
occur in analyzed intronic regions whose functional significance has not yet been determined,
as well as nonsense and frameshift mutations that occur distal to the last known deleterious
amino acid positions of the affected genes.
“Favor Polymorphism” and “Polymorphism”: Includes genetic variants for which available
evidence indicates that the variant is highly unlikely to alter protein production and/or function.
Variants of this type are not reported.
Change of interpretation and issuance of amended reports
The classification and interpretation of all variants identified in the assay reflect the current
state of scientific understanding at the time the report is issued. In some instances, the
classification and interpretation of such variants may change as new scientific information
becomes available.
Whenever there is a change in the classification of a variant that affects the overall
interpretation of a patient’s test result, an amended report will be provided by Myriad.
PERFORMANCE CHARACTERISTICS
Summary of Non-clinical Laboratory Studies
The specific performance characteristics of the myChoice CDx assay were determined by
studies using FFPE tumor samples. Samples were selected to evaluate a range of representative
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tumor BRCA1 and BRCA2 sequence variants (e.g., single nucleotide variants, insertions or
deletions, and variants in homopolymers) and LRs (e.g., deletions and duplications affecting
single and multiple exons) detected by the myChoice CDx assay, as well as a representative
range of GIS, as reflected in the device labeling.
1. Correlation with Orthogonal Reference Method (Accuracy)
The accuracy of the Myriad HRD Status determined by the myChoice CDx test was
demonstrated using a validated Next Generation Sequencing (NGS)-based assay with a
combination of non-clinical samples and FFPE clinical specimens from cancer patients
enrolled in clinical trials from whom sufficient quantity and quality of DNA was available
for testing with the NGS comparator assay. A total of 209 FFPE tumor specimen-derived
DNA samples were tested with both the assays. Samples representing the following
subgroups were tested in the study: 5 tBRCA1/2 Status positive / GIS Status negative, 71
tBRCA1/2 Status negative / GIS Status negative, 66 tBRCA1/2 Status positive / GIS Status
positive, 61 tBRCA1/2 Status negative / GIS Status positive.
a. tBRCA1/2 Sequence Variant and LR Analytical Calls A total of 1,733/1,733 valid BRCA1/2 sequence variant test calls were observed
compared to the valid reference (comparator) BRCA1/2 sequence variant calls with ≥
10% allele frequencies across all samples evaluated. This corresponds to a positive
percent agreement (PPA) of 100%. Including variants with < 10% allele frequency, a
total of 1,733/1,734 valid BRCA1/2 sequence variant calls were observed, corresponding
to a PPA of 99.94% with a 95% lower confidence limit of 99.7267%. In addition, a total
of 3,605,951/3,605,951 valid BRCA1/2 sequence non-variant base calls were observed,
corresponding to a negative percent agreement (NPA) of 100% with a 95% lower
confidence limit of 99.9999%. A total of 402/402 concordant valid BRCA1/2 LR calls
were observed compared to the valid reference (comparator) BRCA1/2 LR calls across all
samples evaluated. This corresponds to an overall percent agreement (OPA) of 100% for
LR calls.
The results of the accuracy study were evaluated for three patient outcomes: (i) the
tBRCA1/2 Status based on BRCA1 and BRCA2 sequence and LR analyses; (ii) the GIS
Status based on the GIS; and (iii) the overall Myriad HRD Status based on the combined
results of the tBRCA1/2 Status and GIS Status. The agreement between the myChoice
CDx device and the comparator (reference) assay is summarized below.
b. tBRCA1/2 Status Results
Concordance analysis of all 200 valid patient results produced by both the myChoice
CDx and Comparator assays resulted in an OPA of 100%.
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c. GIS Status Results
Concordance analysis of all 206 valid patient results produced by both the myChoice
CDx and Comparator assays revealed a PPA of 98.5%, a NPA of 97.4%, and an OPA of
98.1%.
d. Myriad HRD Status Results
Concordance analysis of all 206 valid patient results from both the myChoice CDx and
Comparator assay revealed a PPA of 98.5%, a NPA of 98.6%, and an OPA of 98.5%.
2. Analytical Sensitivity
a. Limit of Blank (LoB)
Twenty-six (26) FFPE normal tissue samples were tested wherein all low frequency
variants were expected to be spurious technical artifacts rather than true biological
events. The distribution of allele frequencies was plotted. The frequencies of spurious
variants were typically very low with the distribution decreasing very rapidly from 1% to
5%. There were no spurious variants with frequency above 5%.
One hundred thirty-six (136) FFPE tBRCA1/2 Status negative (wildtype) tissue samples
were analyzed. These samples produced 2,357,861/2,357,861 (100%) concordant non-
variant base calls, resulting in a false positive rate of 0% with a 95% upper confidence
limit of 0.00013%. Of the 136 samples, 70 samples were both tBRCA1/2 Status negative /
GIS Status negative. These 70 samples produced 1,213,621/1,213,621 (100%) concordant
non-variant base calls, resulting in a false positive rate of 0% with a 95% upper
confidence limit of 0.00025%. This retrospective analysis provides empirical data for
setting a minimum allele frequency threshold of 5% to differentiate spurious background
noise from real variants.
b. Limit of Detection (LoD)
i. tBRCA1/2 Sequence Variants
DNAs from four FFPE samples with known BRCA1/2 pathogenic sequence
variants [BRCA1 c.181T>G (p.Cys61Gly), a single nucleotide variant, BRCA1
c.1961del, a < 10 bp deletion in an 8 bp homopolymer sequence, BRCA1
c.5266dupC, a < 10 bp insertion and BRCA2 c.9117_9117+11del, a ≥ 10 bp
deletion] and FFPE tumor DNA samples without these BRCA1/2 variants (WT)
were used to create simulated tumor:normal DNA samples with 10%, 8%, 6.5%,
5% and 2% allele frequencies of these mutations. Twenty replicates of each of the
various DNA mixes were run and BRCA1/2 sequencing analytical calls were
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analyzed using CLSI’s EP17-A2 probit analysis methods to determine the LoD of
these mutations.
The results of this study show that the LoDs of the four pathogenic sequence
variants have different ranges of allele frequencies. The LoD of a single bp
substitution was at 7.23% allele frequency. The LoD of a < 10 bp deletion in an 8
bp homopolymer sequence was 6.66%. The LoD for a < 10 bp insertion was
6.36%, and the LoD for a ≥ 10 bp deletion was 5.98%.
ii. tBRCA1/2 Large Rearrangements
Two FFPE tumor DNA samples, each carrying a different large rearrangement
(LR): [BRCA1 del exon 8 LR exon and BRCA2 del exons 19–21 LR], were each
mixed with a FFPE DNA with no detectable BRCA1/2 LRs (WT) to create tumor :
normal samples with 50%, 40%, 30% and 10% allele frequencies of each LR. Ten
replicates of each of the various DNA mixes were run and the concordance
between the BRCA1/2 LR test calls and reference calls from each of the undiluted
tumor samples was analyzed. The LoD for each LR was defined based on CLSI’s
EP17-A2 guidance that recommends ≥95% concordant, positive LR calls.
The tBRCA1/2 LR portion of the myChoice CDx assay’s LoD for the ≥ 3 exons
LR is at 30% allele frequency, while the LoD for the 1-2 exons LR is at 50%
allele frequency.
iii. GIS Status
Four FFPE matched tumor-normal samples were evaluated in this LoD study.
DNAs extracted from each pair of FFPE matched tumor and normal samples were
mixed to create five different tumor:normal DNA mixes at 40%, 30%, 20%, 10%
and 0% tumor DNA content. Ten replicates of each of the tumor:normal mixes
were run along with replicates of the undiluted tumor and normal DNAs. All the
tumor:normal DNA mixes were tested using the myChoice CDx assay and final
GIS Status results were analyzed to assess the LoD of this assay.
The results from this LoD study show that the myChoice CDx assay yields highly
valid GIS results and GIS Status results for all samples at all tumor DNA content
levels that produced valid results. Based on this study, the LoD of the GIS portion
of the myChoice CDx assay is at ~ 30% tumor DNA content.
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3. Analytical Specificity
a. Interference (tBRCA1/2 Sequence Variant and LR Analytical Calls)
To evaluate the potential impact of three classes of substances (endogenous [hemoglobin,
triglycerides], exogenous [tissue marking dye, paraffin wax], and method-specific
interferents [ethanol, NaOH]) that can potentially interfere with the assay, this study
evaluated seven FFPE specimens (5 tBRCA1/2 Status positive / GIS Status positive and 2
tBRCA1/2 Status negative / GIS status negative) representing single nucleotide variants,
insertions or deletions of < 10 bp in length, insertions or deletions of ≥ 10 bp in length,
homopolymer variants (5+ bp), and large rearrangements affecting ≥ 3 exons. The effects
of potential interfering substances were tested at one or two replicates to determine if
they would impact the myChoice CDx device, and the results were compared to the
control (no additional interferents) condition.
All treated samples across all six substances at the high test levels passed the acceptance
criteria, with the exception of method-specific NaOH at the high test level (1.0 N), which
failed as 10/14 (71.4%) tests successfully generated valid BRCA1/2 sequencing and LR
results. However, 14/14 (100%) of the tests at the low 0.4 N NaOH level passed. All
samples run under each condition produced valid positive or negative patient calls. The
positive and negative patient calls were 100% concordant when compared to samples
without additional interferents.
b. Interference (GIS)
All treated samples produced valid GIS for each potential interfering substance tested. In
addition, all samples run under each condition produced valid positive or negative patient
calls showing 100% concordance when compared to samples without additional
interferents.
Taken together, these results demonstrate that the tBRCA1/2 sequencing and GIS portions
of the assay are minimally impacted or not impacted by the presence of any of the
substances tested in this study.
Necrosis of ≥ 10% of the tumor area was observed in 11% (n = 66) of tumor samples
from the QUADRA study. Only 3% of samples had necrosis in > 10% of the tumor area,
and no samples were identified with necrosis involving > 60% of the tumor area. The
standard procedure in Myriad’s Anatomic Pathology laboratory is to macro-dissect the
fixed tumor tissues on slides to maximize tumor content, i.e., minimize the inclusion of
non-tumor content including necrotic tissue. Thus, based on the above analysis, it was
concluded that necrosis of ≤ 60% does not impact the myChoice CDx assay results.
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c. Carryover
The purpose of this study was to demonstrate that the myChoice CDx test minimizes
carryover across samples. Fourteen FFPE specimens (11 tBRCA1/2 Status positive / GIS
Status positive, 1 tBRCA1/2 Status positive / GIS Status positive and 2 tBRCA1/2 Status
negative / GIS Status negative) were processed consecutively through DNA extraction.
The DNA from these 14 FFPE samples were then set up in a checkerboard pattern,
alternating between low (50 ng) and high (200 ng) inputs. Two consecutive batches were
set up in this pattern, with one checkboard pattern inversed, to assess intra-run (1st batch)
and inter-run (2nd batch) carryover. An additional reference batch was run with all
samples at 200 ng to compare for concordance. For both the intra-run and inter-run
batches, all 14/14 samples produced complete, valid analytical calls that were 100%
concordant for BRCA1 and BRCA2 sequence and LR calls, and all GIS were valid. In
addition, the patient results of all samples run in both batches were 100% concordant.
Additionally, using the SNVs analyzed in the assay, carryover was quantified within and
between batches. The highest intra-run carryover observed was 0.2% and the highest
inter-run carryover observed was 0.1%. The average intra-run carryover observed was
0.14% and average inter-run carryover was 0.10%. The overall analytical results show
that the myChoice CDx device has very low intra-run and inter-run sample carryover and
poses minimal risk to patient results.
d. Cross-Reactivity
Cross-reactivity studies for sequence-based assays are intended to differentiate between
target analyte sequences and sequences generated from other sources. Three types of
spurious sequences that could potentially be mistaken for target sequences, e.g.,
pseudogenes or other genomic regions that are highly homologous to targeted genes and
regions, off-target regions that hybridize to hybridization baits or DNA sequences that
carry-through the process, and process artifacts and low quality sequences. The purpose
of this study is to demonstrate that captured sequences not originating from target regions
do not materially affect the myChoice CDx test.
Sequencing data for 7 FFPE tissue samples (4 tBRCA1/2 Status positive /GIS Status
positive, 1 tBRCA1/2 Status negative / GIS Status negative, 1 tBRCA1/2 Status negative /
GIS Status positive, and 1 tBRCA1/2 Status unknown / GIS Status positive) were
processed through myChoice CDx in quadruplicate, yielding 28 total tests results that
were mapped to the human genome sequence to reveal off-target sequences due to
pseudogene and cross-reactivity of hybridization baits (capture probes).
The myChoice CDx test has two methods for mitigating the impact of pseudogenes. The
capture baits were designed to minimize the capture of pseudogene regions, and the
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analysis algorithm identifies and excludes pseudogene-derived sequences as part of
BRCA1/2 variant detection and LR calling.
No off-target sequences were found to affect the tumor BRCA1 and BRCA2 component of
the device. Only 1.2% of SNVs used to calculate the GIS were affected by off-target
sequences with a minimal effect on the reported score. This retrospective analysis
suggests that cross-reactivity poses a minimal risk to the myChoice CDx device.
4. Repeatability and Reproducibility
The repeatability and reproducibility of the myChoice CDx was investigated by testing
DNA extracted from FFPE clinical specimens. The purpose of these studies was to
demonstrate that the myChoice CDx assay generates highly reproducible BRCA1 and
BRCA2 sequencing and LR analytical calls and GIS on the tested samples from five
different studies over five periods of time. In the first three studies (Studies 1–3), a total
of 18 unique samples were tested. All but two of these samples were tested at the DNA
input amount of 200 ng per assay. The fourth study (Study 4) evaluated 7 FFPE tumor
specimens from the first three studies at 50 ng DNA input. The samples were run in
duplicate per run, over 6 runs, using 3 lots of reagents, 3 different sets of instruments, 6
different operators, and 3 different data reviewers. An additional study (Study 5) was
performed using 5 unique FFPE samples with 18 replicates per sample divided across 9
independent runs over multiple days using 3 different sequencers and 3 lots of critical
reagents. Thus, a total of 23 FFPE samples were evaluated (10 tBRCA1/2 Status positive /
GIS Status positive, 2 tBRCA1/2 Status positive / GIS Status negative, 6 tBRCA1/2 Status
negative / GIS Status positive, 3 tBRCA1/2 Status negative / GIS Status negative, 2
tBRCA1/2 Status unknown / GIS Status positive). The samples contained single
nucleotide variants, insertions or deletions of < 10 bp in length, insertions or deletions of
≥ 10 bp in length, homopolymer variants (5+ bp), large rearrangements affecting 1-2
exons, and large rearrangements affecting ≥ 3 exons. The tested samples had a wide GIS
range.
a. tBRCA1/2 Sequence Variant and LR Analytical Calls
All 228/228 samples and replicates tested from Studies 1–3 produced complete, valid
BRCA1 and BRCA2 sequencing and LR analytical calls. Overall, 2,220/2,220 BRCA1
and BRCA2 sequence variant calls, 3,951,603/3,951,603 non-variant bases and 456/456
LR calls across all samples/replicates tested were 100% concordant.
Study 4 analyzed 7 FFPE tumor samples at 50 ng DNA inputs, which had previously
been evaluated at 200 ng DNA input levels in Studies 1-3. All samples and replicates run
generated complete (100%) valid BRCA1 and BRCA2 sequence and LR calls. Altogether,
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all 708/708 BRCA1 and BRCA2 sequence variant calls, 1,450,393/1,450,393 non-variant
bases and 168/168 LR calls across all samples/replicates tested at the 50 ng DNA input
level were 100% concordant. All BRCA1 and BRCA2 sequence variant and LR calls from
the 7 samples run at 50 ng DNA inputs were 100% concordant with analytical calls from
the same samples run at 200 ng DNA inputs.
Study 5 tested five new additional ovarian tumor specimens that were tBRCA1/2 Status
negative / GIS Status positive. The specimens were tested at the lowest DNA input of 30
ng with GIS Status being low positives. The myChoice CDx device produced 700/702
concordant BRCA1/2 sequence variant calls, at mean allele frequency (MAF) ≥ 10%,
resulting in a 99.7% PPA. There were two false negative calls in one sample in a single
nucleotide variant with a MAF of 11.2%. When all valid BRCA1/2 sequence variants
were analyzed, including those below 10% MAF, the myChoice CDx device produced
788/792 concordant sequence variant calls resulting in a 99.5% PPA and 99.99%
(1,553,331/1,553,332) concordance for non-variant base calls. For these five samples,
BRCA1/2 LR concordance was 100% (165/165).
b. tBRCA1/2 Status Results
All samples and replicates run for all five studies produced valid positive or negative
patient results, except for two samples, which were inconclusive for the tBRCA1/2 Status
result. However, both of these samples had a positive GIS Status and were therefore both
Myriad HRD Status positive. All valid positive and negative patient calls were 100%
concordant, resulting in 100% PPA and NPA. In addition, valid patient results for all
samples run at 50 ng DNA input level were 100% concordant with their corresponding
sample run at the 200 ng DNA input level.
c. GIS
For the GIS portion of the assay, all 23 samples and replicates at all DNA inputs (200 ng,
50 ng, and 30 ng) from the five studies produced valid GIS. The overall 95% confidence
interval for the true proportion of majority calls across samples correspond to 98.8% -
100% for the first four studies and 81.5% - 100% for the fifth study.
d. GIS Status and Myriad HRD Status Results
All samples and replicates run for all five studies produced complete, valid, positive or
negative patient calls in both sets of patient results. All positive and negative patient calls
were 100% concordant, resulting in 100% PPA and NPA. In addition, all 7 samples run at
the 50 ng and 200 ng DNA input levels were 100% concordant.
These results demonstrate that BRCA1/2 sequence variant and LR calls, GIS, and patient
results of the myChoice CDx assay are highly reproducible across the different process
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and reagent variabilities introduced in these studies.
5. Guardbanding
The myChoice CDx guardband/robustness studies challenged the performance of the
assay across three key parameters: (i) amount of FFPE tumor tissue-derived DNA input
into the myChoice CDx assay, (ii) hybridization temperature for probe capture, and (iii)
library input onto the HiSeq instrument.
For the DNA input guardband study, 28 FFPE tumor samples (13 tBRCA1/2 Status
positive / GIS Status positive, 1 tBRCA1/2 Status positive / GIS Status negative, 4
tBRCA1/2 Status negative / GIS Status positive, 10 tBRCA1/2 Status negative / GIS Status
negative) were run. For the hybridization temperature and library input guardband studies,
seven FFPE tumor samples (3 tBRCA1/2 Status positive / GIS Status positive, 2
tBRCA1/2 Status positive / GIS Status negative, 2 tBRCA1/2 Status negative / GIS Status
negative) were run in triplicate at standard myChoice CDx assay conditions for the
generation of reference results for each guardband condition. All analytical calls (i.e.,
BRCA1/2 sequence variants, LR calls, and GIS) and patient results for the reference and
test samples and replicates were reported.
a. DNA Input Guardband/Robustness
Two studies were performed to evaluate the range of FFPE tumor extracted DNA input
into the assay. In the first study, 14 samples were run in triplicate at 200 ng (used as the
reference), 100 ng and 50 ng, and in singlet at 300 ng, 40 ng, 30 ng, 20 ng, and 10 ng.
The second study ran a different set of 14 samples in triplicate at 200 ng (used as the
reference) and 30 ng. The results from samples with different DNA input and samples
near LoD of the tBRCA1/2 portion (< 10% and ≥ 10% MAF) were reported.
For the tBRCA1/2 portion of the myChoice CDx assay, all valid BRCA1 and BRCA2
sequence variant calls from 300 ng to 10 ng DNA input levels were 99.8% concordant
and all valid BRCA1 and BRCA2 non-variant base calls were 99.99% concordant. All
valid BRCA1 and BRCA2 LR calls produced from 300 ng to 20 ng DNA input levels were
100% concordant (no valid LR calls were produced at the 10 ng input level). For the GIS
portion of the myChoice CDx assay, the total allowable error (TAE) analysis of valid GIS
displayed acceptable amounts of bias and variation by passing pre-defined acceptance
criteria from 300 ng to 30 ng input levels. In addition, the valid patient calls of all tests
run were 100% concordant, except for a single false negative GIS Status patient call in
one out of three replicates of one sample tested at 30 ng. All replicates of this sample had
tBRCA1/2 Status positive patient results, and as such, all patient results were Myriad
HRD Status positive.
b. Hybridization Temperature for Probe Capture
The hybridization temperature for probe capture was evaluated by varying the
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14 MGL CDxDC 0210 REV 3
temperature by ± 1ºC and ± 2ºC from the 65ºC standard condition. Seven FFPE samples
were run at standard hybridization temperature to generate reference results. The results
of the 7 samples from each guardband test condition were compared to the results
obtained at the standard hybridization temperature. All samples across all guardband test
conditions generated complete, valid BRCA1 and BRCA2 sequencing and LR results, as
well as valid GIS. All BRCA1 and BRCA2 sequence and LR calls were 100% concordant.
Additionally, all samples tested at all guardband conditions produced valid GIS analytical
results and all patient results were 100% concordant.
c. Library Input onto the HiSeq Instrument
The library input onto the HiSeq instrument was evaluated by varying the library
concentration by ± 2 pM and ± 4 pM from the 6 pM standard condition. Seven FFPE
samples were run at the standard library input amounts to generate reference results. The
results of the 7 samples from each guardband test condition were compared to the results
obtained at the standard library input amounts. Samples across all guardband test
conditions generated complete, valid BRCA1 and BRCA2 sequencing and LR results, as
well as GIS. All BRCA1 and BRCA2 sequence and LR calls were 100% concordant. All
GIS generated at the different test conditions were valid and passed the pre-defined
acceptance criteria. In addition, all patient results were 100% concordant.
These results show that the myChoice CDx test is robust and is not affected by these
process variations.
6. Stability Studies
a. Stability of FFPE Clinical Specimens
This study evaluated the real-time stability of FFPE tumor blocks and FFPE tumor
sections on slides, stored at laboratory temperature. Reference results were defined from
replicates of each specimen run at the initial (earliest) time point. The analytical and
patient results of aged specimens, run in singlet, were compared to the reference calls for
concordance.
i. FFPE Tumor Blocks
Stability data was analyzed for 16 unique FFPE tumor blocks for up to the 5.5-
year time point. Analytical calls from aged blocks at each time-point were
compared to those from the initial (T0), reference time point. Analytical results
have been obtained for 12, 7 and 6 samples at the 3.5, 5.0, and 5.5 year time
points, respectively. For BRCA1 and BRCA2 sequencing, a single false positive
BRCA2 sequence variant was called at an allele frequency of 8.3% at the 3.5 year
time point. All other BRCA1 and BRCA2 sequence variant calls were 100%
concordant across all aged FFPE tumor blocks tested at each of the time points.
All BRCA1 and BRCA2 LR calls were 100% concordant. In addition, the GIS
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15 MGL CDxDC 0210 REV 3
were valid and patient results were 100% concordant across all aged blocks tested
at the different time points. The stability study has been confirmed up to 5.5
years.
ii. FFPE Tumor Sections
The stability of unique FFPE tumor sections on slides is being evaluated at the
following time points: 0, 1, 3, 5 and 5.5 years. Analytical calls from aged tumor
sections at each testing time-point were compared to those from the initial (T0),
reference time point. At the 1 year time point, all 10/10 samples generated
complete, valid analytical calls and patient results. All BRCA1 and
BRCA2sequence and LR calls were 100% concordant. In addition, all GIS were
valid and all patient results were 100% concordant across all specimens tested.
The stability study has thus far been confirmed up to 1-year time point.
b. FFPE Tumor Extracted DNA Stability
The stability of DNAs extracted from 9 FFPE tumor specimens and stored at -20 ºC was
evaluated at 0 (T0), 30 days, 60 days, 90 days and 6 months. Analytical calls from aged
DNAs at each time-point were compared to those from the initial (T0), reference time
point. All tests performed from 30 days to 6 months produced complete, valid analytical
calls and patient results. For each of the stability testing time points, all BRCA1 and
BRCA2 sequence and LR calls were 100% concordant. In addition, the GIS were valid
and patient results were 100% concordant across all aged FFPE tumor extracted DNAs.
The claimed stability for the extracted DNA is 5 months at -20°C.
c. Reagents Stability
The real-time stability of critical reagents used in the device was evaluated. Three lots of
each of these reagents were stored at specified conditions and run at 0, 1 month, and 4
months. Each reagent lot was tested with 6 FFPE tumor DNAs in duplicate at each aged
reagents time point. Analytical calls from aged reagents at each time-point were
compared to those from the initial (T0) reference time point. All tests performed at 1
month and 4 months produced complete, valid analytical calls and patient results. For
each of the stability testing time points, all BRCA1 and BRCA2 sequence and LR calls
were 100% concordant, the GIS generated were valid, and all the patient results were
100% concordant across all lots of aged reagents.
Summary of Clinical Studies
1. Summary of Clinical Study- Niraparib PR-30-5020-C (QUADRA) for the companion
diagnostic claim.
The niraparib clinical study PR-30-5020-C (QUADRA) was an open-label, single-
arm clinical trial designed to evaluate the efficacy and safety of niraparib in patients
myChoice CDx® Technical Information bit.ly/myChoiceCDxSpecs
16 MGL CDxDC 0210 REV 3
with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube or
primary peritoneal cancer who had received three or more previous chemotherapy
regimens.
a. Accountability of PMA
A total of 728 patients were screened for entry into QUADRA study which resulted in 265 screen-failure and 463 treated patients. Of these 463 patients, 435 niraparib treated patients were included in the PMA cohort. The retrospective analysis included the testing of 590 ovarian FFPE tumor specimens (20 samples were retests from existing patients) from QUADRA where biomarker calls from the CTA were compared with those from the CDx. Therefore, the final PMA cohort by CTA/CDx includes a total of 570 patients: 435 niraparib treated patients, 131 patients who were enrolled and later determined as screen-failures, and 4 patients whose tumor samples were submitted for HRD pre-screening but who were not enrolled into the study.
b. Effectiveness Results
The primary efficacy endpoint was Investigator-assessed confirmed ORR as defined by RECIST (version 1.1). The primary analysis population for this endpoint included all patients with GIS positive tumors who received 3 or 4 prior LOT and whose disease was sensitive to the last platinum based therapy. Patients with prior PARPi treatment were not included in the primary analysis population. The patient’s best overall response (BOR) was determined based on the overall responses at all timepoints between the date of the first dose and the date of first documented radiological disease progression, the date of subsequent anticancer therapy, or the date of study discontinuation, whichever occurred first. Patients with a BOR of either confirmed complete response (CR) or confirmed partial response (PR) were considered to have responded to treatment (“responders”). All other patients were considered not to have responded to treatment (“non-responders”).
Post hoc analyses were also conducted in subgroups defined by platinum sensitivity and biomarkers.
Investigator-assessed confirmed ORR as defined by RECIST (version 1.1) was
analyzed for the biomarker-defined population overall and in the following
biomarker subsets:
• tBRCAm (regardless of platinum sensitivity)
• Non-tBRCA/GIS positive platinum-sensitive
In the biomarker-defined population, meaningful ORR and DOR were observed
among all subgroups, including the following:
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17 MGL CDxDC 0210 REV 3
• In the HRD positive cohort (n=98), the ORR was 24.4% and the median DOR
was 8.3 months.
• In patients with tBRCAm tumors (n=63), the ORR was 28.6% and median
DOR was 9.2 months. When this group was analyzed by platinum sensitivity
status, patients with tBRCAm platinum-sensitive disease (n=18) had an ORR of
38.9%; patients with tBRCAm platinum-resistant disease (n=21) had an ORR of
28.5%; and patients with tBRCAm platinum-refractory disease (n=16) had an
ORR of 18.8%.
• In patients with non-tBRCA/GIS positive platinum-sensitive disease (n=35), the
ORR was 20.0% and median DOR was 6.6 months.
Table 2 Efficacy Results in QUADRA (Biomarker-Defined Population)
Population ORR %
(95% CI)
DOR months
(95% CI)
Biomarker-defined (n=98)
regardless of platinum
sensitivity
24.4% (24/98)
(0.16, 0.34)
8.3
(6.6, not estimable, NE)
tBRCAm (n=63) tumor
regardless of platinum
sensitivity
28.6 % (18/63)
(0.18, 0.41)
9.2
(7.4, NE)
Platinum sensitive (n=18) 38.9% (7/18) (0.17, 0.64)
NE (6.5, NE)
Platinum-resistant (n=21) 28.5% (6/21) (0.11, 0.52)
7.4 (4.7, NE)
Platinum-refractory
(n=16) 18.8% (3/16) (0.04, 0.46
Not estimable
(3.8, NE)
Non-tBRCA/GIS positive
(n=35) platinum sensitive
20.0% (7/35)
(0.08, 0.37)
6.6
(3.5,15.2)
2. Summary of Clinical Study - Niraparib PR-30-5017-C (PRIMA) for maintenance
treatment.
The niraparib clinical study PR-30-5017-C (PRIMA) was a randomized, double-
blind, placebo-controlled, multicenter Phase 3 study design in subjects with ovarian,
fallopian tube, and primary peritoneal cancer, collectively referred to as ovarian
cancer. The objective of PRIMA was to evaluate the therapeutic effect of
maintenance niraparib treatment following response to first-line platinum-based
chemotherapy in patients with advanced ovarian cancer.
a. Accountability of PMA Cohort
A total of 733 patients were screened into the PRIMA study for homologous recombination deficiency (HRD) testing. Test results were
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18 MGL CDxDC 0210 REV 3
required prior to randomization. Subjects with a documented deleterious germline (gBRCA) or somatic (sBRCA) BRCA mutation by local results were considered to have homologous recombination deficient tumors for stratification and randomization purposes; the tumor test was performed concurrently to confirm local results. Of these 733 randomized patients, 487 niraparib-treated and 246 placebo-treated patients were included in the PMA cohort. The retrospective analysis included the testing of 713 ovarian FFPE tumor specimens (7 samples were retests from existing patients and 4 samples from 4 patients who were identified as screen failures after re-matching ID with clinical database) from PRIMA, where biomarker calls from the CTA were compared with those from the CDx. Therefore, the final PMA cohort by CTA/CDx includes a total of 733 patients: 373 HRD positive patients, 249 HRD negative patients, 80 patients who had inconclusive results from HRD testing, and 31 patients without sufficient sample for HRD testing.
b. Effectiveness Results
The primary endpoint was PFS, defined as the time from treatment randomization to the earlier date of assessment of progression (by BICR) or death by any cause in the absence of progression. PFS was based on radiology assessment using RECIST v1.1 criteria. Efficacy analyses were primarily conducted on the intent to treat (ITT) population, in the overall and homologous recombination deficient populations.
The main efficacy conclusions for the prespecified primary analysis population were as follows:
• The study met its primary efficacy objective; treatment with niraparib
prolonged median PFS by 11.5 months compared to placebo in subjects
with homologous recombination deficient advanced ovarian cancer
following response to front-line platinum-based chemotherapy. Median
PFS as determined by BICR based on RECIST (version 1.1) was
21.9 months in the niraparib arm and 10.4 months in the placebo arm (HR
0.43 [95% CI: 0.310,0.588]; p<0.0001).
• In the overall population, treatment with niraparib prolonged median PFS
by 5.6 months compared to placebo. Median PFS as determined by BICR
based on RECIST (version 1.1) was 13.8 months in the niraparib arm and
8.2 months in the placebo arm (HR 0.62 [95% CI: 0.502, 0.755];
p<0.0001).
Table 3 Efficacy Resultsa in PRIMA (Biomarker-Defined Population)
HRD Positive Population Overall Populationb
ZEJULA
(N=247)
Placebo
(N=126)
ZEJULA
(N=487)
Placebo
(N=246)
PFS events, n (%) 81 (33) 73 (58) 232 (48) 155 (63)
myChoice CDx® Technical Information bit.ly/myChoiceCDxSpecs
19 MGL CDxDC 0210 REV 3
PFS Median (95%
CI), in months
21.9
(19.3, NE)
10.4
(8.1, 12.1)
13.8
(11.5, 14.9)
8.2
(7.3, 8.5)
Hazard Ratio (HR)c
(95% CI)
0.43 (0.31, 0.59) 0.62 (0.50, 0.76)
p-valued <0.0001 <0.0001 a efficacy analysis was based on blinded independent central review (BICR). b In the HR proficient (HRD negative) population (N=249), a hazard ratio of 0.68 (95% CI [0.49, 0.94]) was
observed.
In the HR not determined (HRnd) population (N=111), a hazard ratio of 0.85 (95% CI [0.51,1.43]) was
observed. c based on a stratified Cox proportional hazards model d based on a stratified log-rank test
NE=Not Evaluable
3. Summary of Clinical Study - Olaparib NCT03737643 (PAOLA-1) for maintenance
treatment.
The olaparib clinical study was a randomized, double-blind, placebo-controlled,
multi-center trial that compared the efficacy of Lynparza in combination with
bevacizumab versus placebo/bevacizumab for the maintenance treatment of
advanced high-grade epithelial ovarian cancer, fallopian tube or primary peritoneal
cancer following first-line platinum-based chemotherapy and bevacizumab.
a. Accountability of PMA Cohort
Eight hundred and six (806) patients were randomized (2:1) to receive Lynparza tablets 300 mg orally twice daily in combination with bevacizumab (n=537) or placebo/bevacizumab (n=269) who had no evidence of disease (NED) due to complete surgical resection, or who were in complete response (CR), or partial response (PR) following completion of first-line platinum-containing chemotherapy and bevacizumab. Randomization was stratified by first-line treatment outcome (timing and outcome of cytoreductive surgery and response to platinum-based chemotherapy) and tBRCAm status, determined by prospective local testing.
Available tumor samples were retrospectively tested using the myChoice® CDx test to determine HRD positive status, defined by either a deleterious or suspected deleterious BRCA mutation, or a genomic instability score ≥42. 46.7% of patients (376/806) were HRD status positive (26.7% [215/806] were tBRCAm and 20.0% [161/806] were non-tBRCAm) and 33.1% (267/806) were HRD status negative.
A total of 20.2%, (163/806) of patients had an unknown Myriad HRD status (11.5% had no samples available for testing and 8.7% had a cancelled or failed test).
myChoice CDx® Technical Information bit.ly/myChoiceCDxSpecs
20 MGL CDxDC 0210 REV 3
b. Effectiveness Results
The major efficacy outcome measure was investigator-assessed PFS evaluated according to RECIST, version 1.1. PAOLA-1 demonstrated a statistically significant improvement in investigator-assessed PFS for Lynparza/bevacizumab compared to placebo/bevacizumab (HR 0.33; 95% CI 0.25-0.45 with a median of 37.2 months for Lynparza/ bevacizumab vs 17.7 months for placebo/bevacizumab).
Efficacy results from a biomarker subgroup analysis of 387 patients with HRD positive tumors, identified post-randomization using the Myriad myChoice® HRD Plus tumor test, who received Lynparza/bevacizumab (n=255) or placebo/bevacizumab (n=132), are summarized in Table 4. Results from a blinded independent review of PFS were consistent.
Table 4 Efficacy Results – PAOLA-1 (HRD positive status*, Investigator Assessment)
Lynparza/bevacizumab
(n=255)
Placebo/bevacizumab
(n=132)
Progression-Free Survival
Number of events (%) 87 (34%) 92 (70%)
Median, months 37.2 17.7
Hazard ratioa (95% CI) 0.33 (0.25, 0.45)
* Median follow-up of 24.4 months in both treatment arms for censored patients. a The analysis was performed using an unstratified Cox proportional hazards model.
CI Confidence interval
myChoice CDx TRF / 04-20 Myriad, the Myriad logo, Myriad myChoice, Myriad myChoice CDx, and the myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions.
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Test Request Form TO AVOID DELAYS PLEASE COMPLETE ENTIRE FORM
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SPECIMEN RETRIEVAL
I want Myriad Genetic Laboratories, Inc. to request the specimen. (COMPLETE the information below.)
LOCATION OF SPECIMEN PHONE FAX CONTACT NAME
AUTHORIZED SIGNATURE
I hereby authorize testing and confirm that informed consent has been obtained, if required by state law. I hereby attest that the person listed in the Ordering Physician space above is authorized by law in the relevant jurisdiction to order the test(s) requested herein.
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CLINICAL INFORMATION
MYRIAD GENETIC LABORATORIES, INC.320 Wakara Way • Salt Lake City, Utah 84108
Phone: (877) 283-6709Fax: (801) 883-8998Email: myChoiceCDx@Myriad.com
SPECIMEN INFORMATION
Sample Fixative: (check one ):
Fixed tissue Specimen Identification Number as it appears on the tissue block(s) or slides submitted to Myriad:
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# of Block(s): # of Slide(s):
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PATIENT INFORMATION ORDERING PHYSICIAN (Only fill out first line unless new customer or HCP# is unknown)PATIENT NAME (LAST, FIRST, INITIAL) NAME (LAST, FIRST, DEGREE) MYRIAD HCP ACCOUNT #
PATIENT ID # (OPTIONAL) BIRTH DATE (MM/DD/YYYY) NPI # E-MAIL ADDRESS
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Include enlarged copies of both sides of insurance card(s). If two cards are submitted, indicate which is primary.
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TEST REQUESTED
Myriad myChoice® CDx - Next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status, who are eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may become eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with the approved targeted therapy for Lynparza® (olaparib) or Zejula® (niraparib). In addition, detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive Genomic Instability Score in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy.
FOR MEDICARE PATIENTS
ONLY:
AT THE TIME OF BIOPSY OR SURGERY:
Hospital Inpatient (>24 hour stay) Discharge Date: ______________________ (MM/DD/YYYY)
Hospital Outpatient Non-Hospital Patient
Ovarian Cancer (Ovary, Fallopian Tube, Peritoneum) Age at Dx: _______
Date of Biopsy or Surgery: _________________________ (MM/DD/YYYY)
myChoice CDx TRF / 04-20 Myriad, the Myriad logo, Myriad myChoice, Myriad myChoice CDx, and the myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions.
©2020, Myriad Genetics, Inc.
Test Request Form TO AVOID DELAYS PLEASE COMPLETE ENTIRE FORM
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SPECIMEN RETRIEVAL
I want Myriad Genetic Laboratories, Inc. to request the specimen. (COMPLETE the information below.)
LOCATION OF SPECIMEN PHONE FAX CONTACT NAME
AUTHORIZED SIGNATURE
I hereby authorize testing and confirm that informed consent has been obtained, if required by state law. I hereby attest that the person listed in the Ordering Physician space above is authorized by law in the relevant jurisdiction to order the test(s) requested herein.
HEALTHCARE PROVIDER’S SIGNATURE DATE
CLINICAL INFORMATION
MYRIAD GENETIC LABORATORIES, INC.320 Wakara Way • Salt Lake City, Utah 84108
Phone: (877) 283-6709Fax: (801) 883-8998Email: myChoiceCDx@Myriad.com
SPECIMEN INFORMATION
Sample Fixative: (check one ):
Fixed tissue Specimen Identification Number as it appears on the tissue block(s) or slides submitted to Myriad:
Other (describe ):
Tissue Type Submitted (e.g., Ovary):
# of Block(s): # of Slide(s):
Date Specimen Retrieved from Archive:
PATIENT INFORMATION ORDERING PHYSICIAN (Only fill out first line unless new customer or HCP# is unknown)PATIENT NAME (LAST, FIRST, INITIAL) NAME (LAST, FIRST, DEGREE) MYRIAD HCP ACCOUNT #
PATIENT ID # (OPTIONAL) BIRTH DATE (MM/DD/YYYY) NPI # E-MAIL ADDRESS
STREET ADDRESS ADDRESS
CITY STATE ZIP CITY STATE ZIP
DAYTIME PHONE NUMBER E-MAIL ADDRESS OFFICE CONTACT PHONE FAX
Female Male
BILLING/PAYMENT INFORMATION
OPTION 1: PLEASE BILL INSURANCE (For Medicare patients: only available if test order date is more than 2 weeks after discharge date)
Include enlarged copies of both sides of insurance card(s). If two cards are submitted, indicate which is primary.
OPTION 2: PATIENT PAYMENT (Please call Customer Service for questions regarding test prices or for credit card payment)
OPTION 3: Other billing (To establish an account, submit billing information with this form)
Bill our institutional account #: or established research project code #: or Authorization/Voucher #:
TEST REQUESTED
Myriad myChoice® CDx - Next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status, who are eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may become eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with the approved targeted therapy for Lynparza® (olaparib) or Zejula® (niraparib). In addition, detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive Genomic Instability Score in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy.
FOR MEDICARE PATIENTS
ONLY:
AT THE TIME OF BIOPSY OR SURGERY:
Hospital Inpatient (>24 hour stay) Discharge Date: ______________________ (MM/DD/YYYY)
Hospital Outpatient Non-Hospital Patient
Ovarian Cancer (Ovary, Fallopian Tube, Peritoneum) Age at Dx: _______
Date of Biopsy or Surgery: _________________________ (MM/DD/YYYY)
Physician, Bob, MD 2222222Doe, Jane T
00000 x 09/10/1954
123 Generic Street
This City ST 45678
222-000-0000 janedoe@email.com
x
x
x
x
x
x
SIGN & DATE
9/18/2018
10/25/2018
62
Ovary 9324-1234-A
1
10/25/2018
SAMPLE
myChoice CDx SAMPLE TRF/04-20
MGL CDxDC 0194 Rev 3
Once we receive your test, Myriad will automatically replenish your kit supply. If you would like to order additional kits or have any questions about your specimen submission, please call Myriad Customer Service at 877-283-6709.
1. Please select and label at least one formalin-fixed paraffin-embedded tumor block with a cross sectional area ≥ 25mm2 that contains at least 40 microns of tumor. The block should contain at least 20% tumor by pathologic review.
2. Place each tumor block(s) into the provided plastic block holder and cover with an ice pack that has been frozen for 24 hours.
FOR TUMOR BLOCK(S):
myChoice CDx TRF/10-19 Myriad, the Myriad logo, Myriad myChoice, Myriad myChoice CDx, and the myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions. ©2019
MGL CDxDC 0193 rev 0
Test Request Form TO AVOID DELAYS PLEASE COMPLETE ENTIRE FORM
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SPECIMEN RETRIEVAL☐ I want Myriad Genetic Laboratories, Inc. to request the specimen. (COMPLETE the information below.)
LOCATION OF SPECIMEN PHONE
FAX CONTACT NAME
AUTHORIZED SIGNATUREI hereby authorize testing and confirm that informed consent has been obtained, if required by state law. I hereby attest that the person listed in the Ordering Physician space above is authorized by law in the relevant
jurisdiction to order the test(s) requested herein.
HEALTHCARE PROVIDER’S SIGNATURE DATE
CLINICAL INFORMATION
MYRIAD GENETIC LABORATORIES, INC.320 Wakara Way • Salt Lake City, Utah 84108Phone: (877) 283-6709Fax: (801) 883-8998Email: myChoiceCDx@Myriad.com
SPECIMEN INFORMATIONSample Fixative: (check one ):
☐ Fixed tissueSpecimen Identification Number as it appears on the tissue block(s) or slides submitted to Myriad:
☐ Other (describe ):Tissue Type Submitted (e.g., Ovary):
# of Block(s):
# of Slide(s):Date Specimen Retrieved from Archive:
PATIENT INFORMATION
ORDERING PHYSICIAN (Only fill out first line unless new customer or HCP# is unknown)
PATIENT NAME (LAST, FIRST, INITIAL)
NAME (LAST, FIRST, DEGREE) MYRIAD HCP ACCOUNT #
PATIENT ID # (OPTIONAL)
BIRTH DATE (MM/DD/YYYY) NPI # E-MAIL ADDRESS
STREET ADDRESS
ADDRESS CITY
STATE ZIP
CITY
STATE ZIP
DAYTIME PHONE NUMBER E-MAIL ADDRESS
OFFICE CONTACT PHONE
FAXEMAIL
☐ FEMALE☐ MALE
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☐ OPTION 3: OTHER BILLING (To establish an account, submit billing information with this form)☐ Bill our institutional account #: or established research project code #:
or Authorization/Voucher #:
☐ Ovarian Cancer (Ovary, Fallopian Tube, Peritoneum) Age at Dx: _______Date of Biopsy or Surgery: _________________________ (MM/DD/YYYY)
TEST REQUESTED ☐ myChoice® CDx - Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection of BRCA1 and BRCA2 sequencing
and large rearrangement variants and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic
Imbalance (TAI), and Large-scale State Transitions (LST). These results are used to determine homologous recombination deficiency (HRD) positive status associated with treatment
with the targeted therapies.
FOR MEDICARE PATIENTS ONLY:
At the time of biopsy or surgery: ☐ Hospital Inpatient (>24 hour stay) Discharge Date: ______________________ (MM/DD/YYYY)
☐ Hospital Outpatient ☐ Non-Hospital Patient
Include the Test Request Form (TRF) and Pathology Report in the kit.
Specimen InstructionsBLOCKS ARE PREFERRED OVER SLIDES WHENEVER POSSIBLE
1. Please select a formalin-fixed paraffin-embedded tumor block that contains at least 40 microns of tumor. The block should contain at least 20% tumor by pathologic review.
2. Cut and label one 5 micron section for H&E staining ona charged slide.
Cut and label 5 micron sections on uncharged slides according to the table at right:
3. Include Test Request Form (TRF) and Pathology report inthe kit.
FOR SLIDES:
Area of tumor (mm²)
# of 5 µm unstained slides
20-25 8
15-19 12
10-14 16
5-9 20
Myriad, the Myriad logo, Myriad myChoice, the myChoice logo, and myChoice CDx are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions. ©2019, Myriad Genetic Laboratories, Inc
MCCDxTSCSPEC/10-19 MGL CDxDC 0197 Rev0
myChoice CDx TRF/10-19 Myriad, the Myriad logo, Myriad myChoice, Myriad myChoice CDx, and the myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions. ©2019
MGL CDxDC 0193 rev 0
Test Request Form TO AVOID DELAYS PLEASE COMPLETE ENTIRE FORM
This clinician will receive any test cancellation notices and the patient's copy of the test results.
SPECIMEN RETRIEVAL
☐ I want Myriad Genetic Laboratories, Inc. to request the specimen. (COMPLETE the information below.)
LOCATION OF SPECIMEN PHONE
FAX CONTACT NAME
AUTHORIZED SIGNATURE
I hereby authorize testing and confirm that informed consent has been obtained, if required by state law.
I hereby attest that the person listed in the Ordering Physician space above is authorized by law in the relevant
jurisdiction to order the test(s) requested herein. HEALTHCARE PROVIDER’S SIGNATURE DATE
CLINICAL INFORMATION
MYRIAD GENETIC LABORATORIES, INC.
320 Wakara Way • Salt Lake City, Utah 84108
Phone: (877) 283-6709
Fax: (801) 883-8998
Email: myChoiceCDx@Myriad.com
SPECIMEN INFORMATION
Sample Fixative: (check one ):
☐ Fixed tissueSpecimen Identification Number as it appears on the tissue block(s) or slides submitted to Myriad:
☐ Other (describe ):
Tissue Type Submitted (e.g., Ovary):
# of Block(s): # of Slide(s):
Date Specimen Retrieved from Archive:
PATIENT INFORMATIONORDERING PHYSICIAN (Only fill out first line unless new customer or HCP# is unknown)
PATIENT NAME (LAST, FIRST, INITIAL)
NAME (LAST, FIRST, DEGREE) MYRIAD HCP ACCOUNT #
PATIENT ID # (OPTIONAL) BIRTH DATE (MM/DD/YYYY) NPI #
E-MAIL ADDRESS
STREET ADDRESS
ADDRESS
CITY STATE ZIP CITY
STATE ZIP
DAYTIME PHONE NUMBER E-MAIL ADDRESS
OFFICE CONTACT PHONE
FAX
☐ FEMALE☐ MALE
BILLING/PAYMENT INFORMATION
☐ OPTION 1: PLEASE BILL INSURANCE (For Medicare patients: only available if test order date is more than 2 weeks after discharge date)
Include enlarged copies of both sides of insurance card(s). If two cards are submitted, indicate which is primary.
☐ OPTION 2: PATIENT PAYMENT (Please call Customer Service for questions regarding test prices or for credit card payment)
☐ OPTION 3: OTHER BILLING (To establish an account, submit billing information with this form)
☐ Bill our institutional account #: or established research project code #: or Authorization/Voucher #:
☐ Ovarian Cancer (Ovary, Fallopian Tube, Peritoneum) Age at Dx: _______
Date of Biopsy or Surgery: _________________________ (MM/DD/YYYY)
TEST REQUESTED
☐ myChoice® CDx - Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection of BRCA1 and BRCA2 sequencing
and large rearrangement variants and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic
Imbalance (TAI), and Large-scale State Transitions (LST). These results are used to determine homologous recombination deficiency (HRD) positive status associated with treatment
with the targeted therapies.
FOR MEDICARE
PATIENTS ONLY:
At the time of biopsy or surgery:
☐ Hospital Inpatient (>24 hour stay) Discharge Date: ______________________ (MM/DD/YYYY)
☐ Hospital Outpatient ☐ Non-Hospital Patient
BLOCKS ARE PREFERRED OVER SLIDES WHENEVER POSSIBLE
Specimen Instructions
Once we receive your test, Myriad will automatically replenish your kit supply. If you would like to order additional tests or have any questions about your specimen submission, please call Myriad myChoice CDx Customer Service at 1-877-283-6709.
*It is the shipper’s responsibility to ensure that the package containing a diagnostic specimen conforms to FedEx guidelines along with all applicable local, state, federal and international regulations.
Myriad, the Myriad logo, Myriad myChoice, the Myriad myChoice logo, and Myriad Choice CDx are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions.
1. Remove the Myriad Clinical Pack Overwrap bag and the mailing label (found beneath the cardboard tray).
4. If you don’t have a regularly scheduled FedEx pickup, call 800-GO-FEDEX (800-463-3339) to request one. Press “0” and specify that you are shipping with a prepaid air bill.
2. Place completed TEST REQUEST FORM with PATHOLOGY REPORT in the test kit. Please do not write the patient’s name on the test kit.
3. Close the box and place it into the Myriad Clinical Pack Overwrap bag. Affix the enclosed pre-paid mailing label onto the front of the bag.*
Mailing Instructions
MCHRDCDXTSCMAIL/10-19 MGL CDxDC 0199 rev 0
myChoice CDx TRF/10-19 Myriad, the Myriad logo, Myriad myChoice, Myriad myChoice CDx, and the myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc., in the United States and other jurisdictions. ©2019
MGL CDxDC 0193 rev 1
Test Request Form
TO AVOID DELAYS PLEASE COMPLETE ENTIRE FORM
This clinician will receive any test cancellation notices and the patient's copy of the test results.
SPECIMEN RETRIEVAL
☐ I want Myriad Genetic Laboratories, Inc. to request the specimen. (COMPLETE the information below.)
LOCATION OF SPECIMEN
PHONE
FAX
CONTACT NAME
AUTHORIZED SIGNATURE
I hereby authorize testing and confirm that informed consent has been obtained, if required by state law.
I hereby attest that the person listed in the Ordering Physician space above is authorized by law in the relevant
jurisdiction to order the test(s) requested herein.
HEALTHCARE PROVIDER’S SIGNATURE DATE
CLINICAL INFORMATION
MYRIAD GENETIC LABORATORIES, INC.
320 Wakara Way • Salt Lake City, Utah 84108
Phone: (877) 283-6709
Fax: (801) 883-8998
Email: myChoiceCDx@Myriad.com
SPECIMEN INFORMATION
Sample Fixative:
(check one ):
☐ Fixed tissue
Specimen Identification Number as it appears on the tissue block(s) or slides submitted to Myriad:
☐ Other (describe ):
Tissue Type Submitted (e.g., Ovary):
# of Block(s):# of Slide(s):
Date Specimen Retrieved from Archive:
PATIENT INFORMATION
ORDERING PHYSICIAN (Only fill out first line unless new customer or HCP# is unknown)
PATIENT NAME (LAST, FIRST, INITIAL)
NAME (LAST, FIRST, DEGREE)
MYRIAD HCP ACCOUNT #
PATIENT ID # (OPTIONAL)
BIRTH DATE (MM/DD/YYYY) NPI #
E-MAIL ADDRESS
STREET ADDRESS
ADDRESS
CITY
STATE ZIP
CITY
STATE ZIP
DAYTIME PHONE NUMBER
E-MAIL ADDRESS
OFFICE CONTACT
PHONE FAX
☐ FEMALE
☐ MALE
BILLING/PAYMENT INFORMATION
☐ OPTION 1: PLEASE BILL INSURANCE (For Medicare patients: only available if test order date is more than 2 weeks after discharge date)
Include enlarged copies of both sides of insurance card(s). If two cards are submitted, indicate which is primary.
☐ OPTION 2: PATIENT PAYMENT (Please call Customer Service for questions regarding test prices or for credit card payment)
☐ OPTION 3: OTHER BILLING (To establish an account, submit billing information with this form)
☐ Bill our institutional account #: or established research project code #:
or Authorization/Voucher #:
☐ Ovarian Cancer (Ovary, Fallopian Tube, Peritoneum) Age at Dx: _______
Date of Biopsy or Surgery: _________________________ (MM/DD/YYYY)
TEST REQUESTED
☐ myChoice® CDx - A next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection of BRCA1 and BRCA2 sequencing and large rearrangement
variants and the determination of genomic instability status (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and
Large-scale State Transitions (LST). These results are used to determine positive homologous recombination deficiency (HRD) status associated with treatment with the approved
targeted therapies.
FOR MEDICARE
PATIENTS ONLY:
At the time of biopsy or surgery:
☐ Hospital Inpatient (>24 hour stay) Discharge Date: ______________________ (MM/DD/YYYY)
☐ Hospital Outpatient ☐ Non-Hospital Patient
CONFIDENTIAL
MMM523294
Myriad myChoice® CDx Test Result
ORDERING HEALTHCARE PROVIDERBobby Doctor PhDThe Doctor's Place123 Street NameAnywhere, UT 84101
PATHOLOGY Jonny Pathologist PhD
SPECIMENSpecimen Type:Tissue:Surgery/Biopsy Date:TRF Received:Sample Received:
Tissue BlockOvaryMar 13, 2019Oct 1, 2019Oct 1, 2019
Report Date: Oct 23, 2019
PATIENTLast Name:First Name:Date of Birth:Patient ID:Gender:Accession #:Requisition #:
Pt Last NamePt First NameJan 7, 1967Patient idFemale08000148-BLD08000148
Myriad Genetic Laboratories, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 877-283-6709 FX: 801-883-8998Myriad, the Myriad logo, Myriad myChoice, and the Myriad myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and other jurisdictions © 2019. Lynparza is a registered trademark of AstraZeneca group of companies. Zejula is a registered trademark of GSK. MGL CDxDC 0201 Rev 3
Block(s) Analyzed: 132test-1
Myriad HRD Status: POSITIVE
GIS Status: POSITIVEThe Genomic Instability Score (GIS) is a measurement of three biomarkers (loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions) associated with homologous recombination deficiency.
Tumor Mutation BRCA1/BRCA2 Status: POSITIVE FOR A CLINICALLY SIGNIFICANT MUTATION
GENE CLINICALLY SIGNIFICANT MUTATION(S) INTERPRETATION
BRCA1 c.2433del (p.Lys812Argfs*3) Deleterious
NOTE: This result represents findings from all analyzable regions. It may or may not reflect the germline status of this individual. Follow-upgermline testing may be appropriate. In addition, the variants listed above may not be present in all tumor cells.
ASSAY DESCRIPTION
Intended Use: Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens.
The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status, who are eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may become eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with the targeted therapy listed in Table 1 in accordance with the approved therapeutic product labeling.
TABLE 1: Companiondiagnostic indications
Tumor Type Biomarker TherapyOvarian Cancer Myriad HRD (defined as deleterious or
suspected deleterious mutations in BRCA1 and BRCA2 genes and/or positive GenomicInstability Score )
Zejula® (niraparib)
(olaparib)
Detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive Genomic Instability Score in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, Inc., a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108
This Authorized Signature pertains to this laboratory report: Benjamin B. Roa, PhD
Diplomate ABMGGLaboratory Director
Karla Bowles, PhDDiplomate ABMGGLaboratory Director
Hillary Zalaznick, MDDiplomate FCAPLaboratory DirectorAnatomic Pathology
page 1 of 2
Lynparza®
CONFIDENTIAL
MMM523293
Myriad myChoice® CDx Test Result
ORDERING HEALTHCARE PROVIDERBobby Doctor PhDThe Doctor's Place123 Street NameAnywhere, UT 84101
PATHOLOGY Jonny Pathologist PhD
SPECIMENSpecimen Type:Tissue:Surgery/Biopsy Date:TRF Received:Sample Received:
Tissue BlockOvaryMar 13, 2019Oct 1, 2019Oct 1, 2019
Report Date: Oct 23, 2019
PATIENTLast Name:First Name:Date of Birth:Patient ID:Gender:Accession #:Requisition #:
Pt Last NamePt First NameJan 7, 1968Patient idFemale08000147-BLD08000147
Myriad Genetic Laboratories, Inc. | 320 Wakara Way, Salt Lake City, Utah 84108 | PH: 877-283-6709 FX: 801-883-8998 Myriad, the Myriad logo, Myriad myChoice, and the Myriad myChoice CDx logo are either trademarks or registered trademarks of Myriad Genetics,Inc. in the United States and other jurisdictions © 2019. Lynparza is a registered trademark of AstraZeneca group of companies. Zejula is a registered trademark of GSK. MGL CDxDC 0202 Rev 3
Block(s) Analyzed: 12test3-1
Myriad HRD Status: NEGATIVE
GIS Status: NEGATIVEThe Genomic Instability Score (GIS) is a measurement of three biomarkers (loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions) associated with homologous recombination deficiency.
Tumor Mutation BRCA1/BRCA2 Status: NEGATIVE FOR A CLINICALLY SIGNIFICANT MUTATION
ASSAY DESCRIPTIONIntended Use: Myriad myChoice® CDx is a next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of Genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens.
The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status, who are eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes, or may become eligible, because of a positive test result for deleterious or suspected deleterious mutations in BRCA1 or BRCA2 genes or a positive Genomic Instability Score, for treatment with the targeted therapy listed in Table 1 in accordance with the approved therapeutic product labeling.
TABLE 1: Companiondiagnostic indications
Tumor Type BiomarkerOvarian Cancer Myriad HRD (defined as deleterious or
suspected deleterious mutations in BRCA1 and BRCA2 genes and/or positive Genomic Instability Score)
Therapy Lynparza® (olaparib)
Detection of deleterious or suspected deleterious BRCA1 and BRCA2 mutations and/or positive Genomic Instability Score in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula® (niraparib) maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, Inc., a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108
This Authorized Signaturepertains to this laboratory report:
Benjamin B. Roa, PhDDiplomate ABMGGLaboratory Director
Karla Bowles, PhDDiplomate ABMGGLaboratory Director
Hillary Zalaznick, MDDiplomate FCAPLaboratory DirectorAnatomic Pathology
page 1 of 2
Zejula® (niraparib)
NOTE: This result represents findings from all analyzable regions. It may or may not reflect the germline status of this individual.
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